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GSE4883
Homo sapiens
9 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
HMG-CoA reductase inhibitors, statins, have beneficial vascular effects beyond their cholesterol-lowering action. These pleiotropic effects include an anti-inflammatory effect on macrophages. Since macrophages play a central role in atherogenesis, we further characterized the effects on peripheral blood monocyte-macrophages (HPBM). Using Affymetrix gene chip analysis of simvastatin-treated HPBM, we found that simvastatin treatment lead to the downregulation of the expression of many proinflammatory genes including several chemokines (e.g. MCP-1, MIP-1 alpha and , RANTES, several other CC and CXC chemokines, IL-2 receptor-, and leukemia inhibitory factor), members of the tumor necrosis factor family (e.g. lymphotoxin beta and TRAIL), VCAM-1, ICAM-3, and tissue factor (TF). Simvastatin also modulated the expression of several transcription factors essential for the inflammatory response: simvastatin downregulated the expression of NF-kappaB relA/p65 subunit and ets-1 transcription factor, and upregulated the expression of a novel atheroprotective transcription factor, Kruppel-like factor 2 (KLF-2). The effects of simvastatin on KLF-2 and its target genes were dependent on protein prenylation, since inhibitors of protein prenylation had a similar inhibitory effect in THP-1 derived macrophages. Additionally, by lentiviral overexpression KLF-2 we showed that the effect of simvastatin on MCP-1 and TF were dependent on KLF-2. We concluded that simvastatin had a strong anti-inflammatory effect on macrophages, which includes upregulation of the atheroprotective transcription factor KLF-2. These findings further explain the beneficial pleiotropic effects of statins on cardiovascular diseases.
Publication Title
Simvastatin has an anti-inflammatory effect on macrophages via upregulation of an atheroprotective transcription factor, Kruppel-like factor 2.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background and Purpose
Publication Title
Upregulated signaling pathways in ruptured human saccular intracranial aneurysm wall: an emerging regulative role of Toll-like receptor signaling and nuclear factor-κB, hypoxia-inducible factor-1A, and ETS transcription factors.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Paired samples from human femoral artery lesions were obtained during intravascular surgery exploiting Silverhawk device
Publication Title
Global DNA methylation analysis of human atherosclerotic plaques reveals extensive genomic hypomethylation and reactivation at imprinted locus 14q32 involving induction of a miRNA cluster.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 55 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SCANB SubSeries listed below.
Publication Title
The Sweden Cancerome Analysis Network - Breast (SCAN-B) Initiative: a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 55 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Breast cancer exhibits significant molecular, pathological, and clinical heterogeneity. Current clinicopathological evaluation is imperfect for predicting outcome, which results in overtreatment for many patients, and for others, leads to death from recurrent disease. Therefore, additional criteria are needed to better personalize care and maximize treatment effectiveness and survival. To address these challenges, the Sweden Cancerome Analysis Network - Breast (SCAN-B) consortium was initiated in 2010 as a multicenter prospective study with longsighted aims to 1) analyze breast cancers with next-generation genomic technologies for translational research in a population-based manner and integrated with healthcare; 2) decipher fundamental tumor biology from these analyses; 3) utilize genomic data to develop and validate new clinically-actionable biomarker assays; and 4) build the infrastructure for real-time clinical implementation of molecular diagnostic, prognostic, and predictive tests. In the first phase, we focus on molecular profiling by next-generation RNA-sequencing on the Illumina platform. In the three years from August 30, 2010 through August 31, 2013, we have consented and enrolled 3,979 patients with primary breast cancer at the seven hospital sites in South Sweden, representing approximately 85% of eligible patients in the catchment area. Pre-operative blood samples have been collected for 3,942 (99%) patients and primary tumor specimens collected for 2,929 (74%) patients. Herein we describe the study infrastructure and present initial proof of concept results from prospective RNA-sequencing including tumor molecular subtyping and detection of driver gene mutations. We demonstrate that large-scale population-based collection and RNA-sequencing analysis of breast cancer is feasible. The SCAN-B Initiative should significantly reduce the time to discovery, validation, and clinical implementation of novel molecular diagnostic and predictive tests. We welcome the participation of additional comprehensive cancer treatment centers.
Publication Title
The Sweden Cancerome Analysis Network - Breast (SCAN-B) Initiative: a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
NextSeq 500
Description
The X-linked DDX3X gene encodes an ATP-dependent DEAD-box RNA helicase frequently altered in various human cancers including melanomas. Despite its important roles in translation and splicing, how DDX3X dysfunction specifically rewires gene expression in melanoma remains completely unknown. Here we uncover a DDX3X-driven post-transcriptional program that dictates melanoma phenotype and poor disease prognosis. Through an unbiased analysis of translating ribosomes we identified the microphtalmia-associated transcription factor, MITF, as a key DDX3X translational target that directs a proliferative-to-metastatic phenotypic switch in melanoma cells. Mechanistically, DDX3X controls MITF mRNA translation via an internal ribosome entry site (IRES) embedded within the 5' untranslated region. Through this exquisite translation-based regulatory mechanism, DDX3X steers MITF protein levels dictating melanoma metastatic potential in vivo and response to targeted therapy. Together these findings unravel a post-transcriptional layer of gene regulation that may provide a unique therapeutic vulnerability in aggressive male melanomas. Overall design: We sequenced transcripts associated with translationally active ribosomes (polysomes) isolated by sucrose gradient fractionation from DDX3X and control siRNA-transduced HT144 cells. Experiments were performed in duplicates.
Publication Title
The X-Linked DDX3X RNA Helicase Dictates Translation Reprogramming and Metastasis in Melanoma.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This study is part of a larger effort set to determine the factors requried for the crosstalk between tumor cells and fibroblasts in breast cancer.
Publication Title
Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Microarray was used to study global gene expression of a cell culture model based on SV40-immortalized human corneal epithelial (iHCE) cells. The gene expression profile of the cell line was compared to the normal human corneal epithelium. Affymetrix HG-U133A GeneChips were used for microarray experiments and results were validated by performing RT-qPCR for selected genes. iHCE was found to over- and under-express 22 % and 14 % of the annotated genes, respectively. The results of this study suggest that differences between iHCE cells and normal corneal epithelium are substantial and therefore the use of these cells in corneal research should be considered with caution.
Publication Title
Gene expression analysis in SV-40 immortalized human corneal epithelial cells cultured with an air-liquid interface.
Sample Metadata Fields
Cell line
View Samples